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Conversations with the Director: Michael Shaw

Flu Would be a Lousy Bioterrorism Agent

Michael Shaw says, "CDC has been part of the global flu program for more than 60 years. I think with the recognition that flu spreads so quickly, it’s an international issue. If an organism doesn't spread quickly, the urgency isn’t there."

CDC Director Tom Frieden, MD, MPH recently launched a new initiative called Conversations with the Director. The third participant was microbiologist Michael Shaw, PhD, associate director of Laboratory Science for the Influenza Division.

Once a month, Frieden meets with a CDC employee to discuss his or her public health work. “I love these conversations because I get to learn more about the great work CDC scientists do,” said Frieden.

Staff can be nominated by senior leadership to participate in Conversations with the Director. If you are interested, contact your senior leaders to submit your name or the name of someone else you think would be good for this series.

Facts about Flu

Influenza, or flu, is a contagious respiratory illness caused by flu viruses that infect the nose, throat, and lungs. It can cause mild to severe illness, and can lead to death. There are many different influenza viruses that are constantly changing, and immunity isn’t always very long-lasting; hence the need for a new flu vaccine every year.

Flu illness can vary from mild to severe. You’re more likely to have severe symptons, depending on your age and any other conditions you have, such as asthma (even mild or controlled), neurological and neurodevelopmental conditions, chronic lung disease, heart disease, blood disorders, endocrine disorders (such as diabetes), kidney, liver, and metabolic disorders, and weakened immune systems due to disease or medication.

Scientists believe that flu viruses spread mainly by droplets made when people with the flu cough, sneeze or talk. These droplets can land in the mouths or noses of people who are nearby.

Fate Decided to Intervene

Shaw was in graduate school at the University of Alabama in Birmingham, which required him to rotate through three different labs as a way of getting students acclimated and helping them discover what area they wanted to pursue. The year was 1976 and Shaw was doing his rotation in the influenza lab when samples from Fort Dix were shown to be an H1N1 strain of “swine influenza.” “I happened to be in the flu lab at the time. And it’s like everything came together. I thought, wow, flu is pretty interesting—got into it and never left.”

Once out of graduate school, Shaw did his post-doctoral work at Rockefeller University under Punell Choppin. Choppin decided to leave to head the Howard Hughes Medical Institute. “The Rockefeller is set up like the old European system; if the head of the lab leaves, everybody has to leave because he’s the only tenured one. And I was recruited to come here [to CDC as a visiting scientist in 1985 and stayed here for three years, then went to the faculty of the University of Michigan because they were trying to establish a new molecular epidemiology program in the School of Public Health.”

Shaw was at the University of Michigan for five years, teaching mainly flu, but other viruses as well. “My students were working` on RSV, HPV, HIV – I had to be a jack-of-all-trades in a situation like that. In 1993, a permanent position opened up here and I was recruited back by Nancy Cox. And I’ve been here ever since.”

Pandemic Strikes

Shaw holding discussions with the Field Epidemiology Training Program participants in Khyber-Pakhtunkhwa Province, Pakistan.

Talk between Frieden and Shaw moved from their beginnings in public health to a time when Frieden called New York City home, and CDC was facing the first pandemic of the new century. “What is your most vivid memory of H1N1?” he asked Shaw.

Shaw said that it was the shock that “it was in our backyard. We were all expecting flu to emerge from Southeast Asia, not Mexico—and with some advance warning.” Shaw recalled that, ironically, it was a machine that CDC and BARDA were trying to get to market that first detected the novel flu strain. “I remember that coming through very well.” He also recalled taking his grandsons back to their parents’ house and conducting conference calls from the dining room table. It was around spring break when the first US cases appeared. He had to tell his grandsons he was returning to Atlanta to help figure out what was going on.

“After that, it just makes you proud to see the way that people pulled together. The hours people put into this— everybody was running on adrenaline. It got to the point where Rich Besser was telling people they had to take a weekend off. It wasn’t that they had to work, it’s that they wanted to; they wanted to know what was going on. They wanted to figure it out. Was it just California, Texas, New York City?”

Frieden shared his experience of those weeks: “I remember, we had this huge outbreak at a high school in Queens. The school system went nuts. And Mayor Bloomberg was very involved. I remember being in a meeting with him and telling him, ‘we’ve sent the specimens to CDC.’ And he said, ‘Why can’t we do them in our labs?’ And I had to explain that this was a new test, that it didn’t exist a couple days ago. The work that your lab was doing then was amazing.”

Frieden was talking about the reagent work Shaw’s lab was performing – and at a faster than normal pace. Shaw said shortly before the pandemic began, the Influenza Division, one of the collaborating centers making up the World Health Organization’s Global Influenza Surveillance and Response System, had just begun deploying real time PCR testing for the WHO system, using diagnostic kits they supplied to labs domestically and globally. Because the CDC lab is a part of the WHO flu surveillance system, they had been developing flu reagents for years, including swine flu reagents, and they were able to quickly produce and distribute diagnostic kits to labs like Frieden’s in New York City, which desperately needed them. The Influenza Division lab was constantly updating and improving the diagnostic kit throughout the summer.

Next Steps

Shaw during an encounter with a cobra in the souq of Marrakesh, Morocco.

After the excitement around the lab because of H1N1, Frieden asked what Shaw and his colleagues are working on now.

“There’s always something going on in the lab,” Shaw said. He and his group are looking at a risk assessment of new strains as they appear, as well as receptor binding, transmission studies in ferrets (“which is very popular with the media,” Shaw said), drug development, monitoring resistance, and developing assays. The conversation turned to another media-worthy issue: dual use. In December 2011 the National Science Advisory Board for Biosecurity recommended a moratorium on two studies regarding H5N1 or bird flu.

“I think, in this case, the concern is understandable. The talk about flu as a bioterrorism agent is off base, though,” Shaw said. “Flu would be a lousy bioterrorism agent. You can’t put it in an envelope or spray it out of a plane. Now, the accidental release issue is probably a legitimate concern. Lab accidents have happened and are going to happen. We’re very careful here at CDC, but lab workers are human and there are a lot of people working on flu worldwide. Information should be released, mutations need to be known. People in the hot spots need to know what to look for if there is a strange die-off of birds. It could act as an alert.” But Shaw recommends caution. Scientists have been discussing this topic for a while and though the original moratorium has expired, CDC is still observingt.observing it.

Frieden noted that CDC and Shaw’s lab performed stellar work during H1N1 and were an excellent source of information during H1N1 and since.

Shaw says, “CDC has been part of the global flu program for more than 60 years. I think with the recognition that flu spreads so quickly, it’s an international issue. If an organism doesn’t spread quickly, the urgency isn’t there.”

Future of Flu

The conversation moved to the future of flu and what we’ll see next – and Shaw said genomic sequencing. Before, sequencing a whole gene could be a long-term graduate student project, Shaw said, but now we can sequence multiple genes in one afternoon. Shaw described the machine that does the sequencing (“It’s as big and wide as this conference table,” Shaw said) and how, because of the amount of data that comes off it, the machine has a dedicated computer network. It’s the science of bioinformatics, how computer technology, medicine and science mix. And Shaw has been involved in CDC’s bioinformatics discussions since the beginning.

“When we do sequencing, there are huge amounts of data. The bioinformatics capacity requirement is huge. But then you have big questions, like patient privacy, since host genome information is also there in a clinical specimen. Do you sequester it? How valuable is that host genomic information in there?”

“That poses a very interesting question about transparency. And it goes back to one of our responsibilities, to base all public health decisions on the highest quality scientific data, openly and objectively derived,” Frieden said.

“This is the issue of the future,” Shaw said. “How to handle data. Because real time PCR is great, but it’s targeted. These third and fourth generations of sequencing give you the advantage of seeing everything. Before, we were going by suspicion about what pathogen was in a specimen. Now, we can ask, ‘What else might be there?’”

Shaw noted that with the costs of sequencing coming down, this technology will likely make it to clinicians’ offices. And that, Shaw said, “brings up another problem we can’t lose sight of – a lot of these molecular techniques are inherently destructive techniques. You don’t have organisms left. We have to remember to encourage labs to continue to use the classic methods of microbiology, like culturing the pathogens. We have to be careful not to go too far one way.”